Peroxisome proliferator-activated receptors as attractive antiobesity targets.

The peroxisome proliferator-activated receptors (PPARs) alpha, delta and gamma are a group of ligand-activated transcription factors that function as lipid sensors and govern numerous biological processes, including energy metabolism, cell proliferation, differentiation and inflammation. It has been known for some time that both PPAR alpha and PPAR gamma play a role in lipid metabolism. Antidiabetic drugs of the thiazolidinedione (TZD) class are potent and selective activators of PPAR gamma known to promote adipocyte differentiation and lipid storage. Lipid-lowering agents of the fibrate class activate PPAR alpha. Until recently, the function of PPAR delta remained elusive, but recent progress has shown that PPAR delta plays a key role in lipid metabolism, as it regulates serum lipid profiles and fatty acid beta oxidation in muscle and adipose tissue. This suggests that PPAR delta agonists may play a beneficial role in the treatment of lipid disorders, in particular obesity. This review will highlight key new findings in PPAR delta biology and discuss the recent evidence linking PPAR alpha and PPAR gamma to adipose tissue biology and the development of obesity.